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Title: Focal induction of IGF binding proteins in proximal tubules of diabetic rat kidney.
Austin Authors: Bach, Leon A;Cox, Allison J;Mendelsohn, Frederick AO;Herington, A C;Werther, G A;Jerums, George 
Affiliation: Department of Medicine, Austin Hospital, Heidelberg, Victoria, Australia
Issue Date: 1-Apr-1992
Publication information: Diabetes; 41(4): 499-507
Abstract: Diabetes-associated kidney enlargement is associated with increased kidney insulinlike growth factor I (IGF-I) binding. IGF-I binds to the type I IGF receptor, which mediates most of its actions, and to specific binding proteins (IGFBPs), which modulate its actions. To explore the nature and extent of IGF-I binding in the kidney, in vitro autoradiography was used to map the distribution of IGF binding in control and diabetic rat kidney. Specificity studies were performed with increasing concentrations of unlabeled IGF-I, IGF-II, des(1-3)IGF-I (an IGF-I derivative that binds to receptors normally but with decreased affinity to binding proteins), and insulin. In control rats, diffuse binding was found throughout the kidney with increased density in the papilla. Binding specificity in the cortex and outer medulla was typical of the type I IGF receptor (IGF-I = des[1-3]IGF-I greater than IGF-II much greater than insulin). Binding in the outer medulla of diabetic kidney was typical of the type I IGF receptor. A marked focal increase in proximal tubular binding occurred in 13 of 22 postpubertal diabetic rats. Binding specificity of the proximal tubular binding was consistent with the predominance of an IGF binding protein (IGF-I = IGF-II greater than des[1-3]IGF-I with minimal displacement by insulin). Northern-blot analysis revealed increased IGFBP-1 and IGFBP-3 mRNA in cortical tissue from diabetic rats displaying increased proximal tubular binding but not from diabetic rats not displaying this phenomenon. As cell surface association of IGFBPs is linked to potentiation of IGF activity, a possible mechanism for potentiation of local IGF-I action may be provided.
Gov't Doc #: 1376703
Type: Journal Article
Subjects: Animals
Blotting, Northern
Carrier Proteins.analysis.genetics.metabolism
Cell Membrane.chemistry.ultrastructure
Diabetes Mellitus, Experimental.genetics.metabolism
Insulin-Like Growth Factor Binding Proteins
Insulin-Like Growth Factor I.analysis.metabolism
Insulin-Like Growth Factor II.analysis.metabolism
Iodine Radioisotopes
Kidney Tubules, Proximal.chemistry.metabolism.ultrastructure
Protein Binding
Rats, Inbred Strains
Receptors, Cell Surface.analysis.metabolism
Receptors, Somatomedin
Appears in Collections:Journal articles

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